Endothelial nitric oxide synthase gene polymorphisms associated with susceptibility to high altitude pulmonary edema in Chinese railway construction workers at Qinghai-Tibet over 4 500 meters above sea level.

OBJECTIVE: To examine whether the polymorphisms of endothelial nitric oxide synthase (eNOS) gene are associated with the susceptibility to high altitude pulmonary edema (HAPE) in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level. METHODS: A case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat (VNTR) in intron 4, were genotyped using polymerase chain reaction (PCR) and confirmed with DNA sequencing. RESULTS: The frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group (P=0.0028 and P=0.0047, respectively). However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes (H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR) were significantly higher in HAPE patients (both Pü0.0001). On the contrary, the frequencies of H1 (T-G-b) and H2 (T-G-a) were lower in HAPE patients than in healthy controls (both Pü0.001). CONCLUSIONS: Two haplotypes (T-T-b and C-G-a) may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.

Inhibitory effects of alpha-zearalenol on angiotensin II-induced integrin beta3 mRNA via suppression of nuclear factor-kappaB / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effect of alpha-zearalenol on angiotensin II-induced beta3 integrin mRNA expression in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>The mRNA level in integrin beta3 was determined by reverse transcription-polymerase chain reaction. Endothelial NF-kappaB activity was determined by the luciferase activity assay of plasmid NF-kappaB-LUC.</p><p><b>RESULTS</b>The angiotensin II-induced beta3 integrin mRNA expression was inhibited by alpha-zearalenol and 17beta-estradiol (10 nmol/L -1 micromol/L), but not influenced by ICI 182, 780, a pure competitive antagonist for estrogen receptor or a nitric oxide inhibitor Nomega-Nitro-L-arginine methyl ester hydrochloride. Alpha-zearalenol and 17beta-estradiol suppressed the angiotensin II-induced activation of NF-kappaB in endothelial cells.</p><p><b>CONCLUSION</b>Alpha-zearalenol inhibits angiotensin II-induced integrin beta3 mRNA expression by suppressing NF-kappaB activation in endothelial cells.</p>

mRNA expression of muscarinic receptors in spinal cord and brainstem in morphine dependent rats / 药学学报

<p><b>AIM</b>To observe mRNA expression of muscarinic acetylcholine receptors in spinal cord and brainstem in morphine dependent or withdrawal rats.</p><p><b>METHODS</b>The mRNA expression level of m1, m2, m3, m4 and m5 were determined by RT-PCR, the beta-actin mRNA expression was used as internal control.</p><p><b>RESULTS</b>The mRNA level of m1, m2, m3, m4 and m5 in spinal cord and m1 and m2 in brainstem were increased significantly during morphine dependence, and the levels of m1, m2, m3 and m4 in spinal cord and m1 in brainstem were decreased 1 h after the injection of naloxone (4 mg.kg-1, i.p.) in morphine dependent rats. Either scopolamine (0.5 mg.kg-1) or pirenzepine (10 mg.kg-1) was shown to significantly decrease the morphine withdrawal symptoms in rats. The levels of m1, m2, m3 and m5 in spinal cord were increased by pretreatment with pirenzepine and the levels of m2, m3 and m4 in spinal cord were increased by pretreatment with scopolamine.</p><p><b>CONCLUSION</b>The adaptive expression of muscarinic receptors at spinal and supraspinal levels play important role in mediating morphine dependence and withdrawal in rats.</p>